How Many Cell Types Are in the Kidney and What Do They Do?

The kidney maintains electrolyte, water, and acid-base balance, eliminates foreign and waste compounds, regulates blood pressure, and secretes hormones. There are at least 16 different highly specialized epithelial cell types in the mammalian kidney. The number of specialized endothelial cells, immune cells, and interstitial cell types might even be larger. The concerted interplay between different cell types is critical for kidney function. Traditionally, cells were defined by their function or microscopical morphological appearance. With the advent of new single-cell modalities such as transcriptomics, epigenetics, metabolomics, and proteomics we are entering into a new era of cell type definition. This new technological revolution provides new opportunities to classify cells in the kidney and understand their functions.

Use of Race in Kidney Function Estimation: Lessons Learned and the Path Toward Health Justice.

In 2020, the nephrology community formally interrogated long-standing race-based clinical algorithms used in the field, including the kidney function estimation equations. A comprehensive understanding of the history of kidney function estimation and racial essentialism is necessary to understand underpinnings of the incorporation of a Black race coefficient into prior equations. We provide a review of this history, as well as the considerations used to develop race-free equations that are a guidepost for a more equity-oriented, scientifically rigorous future for kidney function estimation and other clinical algorithms and processes in which race may be embedded as a variable.

Shared genetic effect of kidney function on bipolar and major depressive disorders: a large-scale genome-wide cross-trait analysis.

BACKGROUND: Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation. METHODS: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium. RESULTS: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD. CONCLUSIONS: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.

Creatinine clearance is maintained in a range of wet-bulb globe temperatures and work-rest ratios during simulated occupational heat stress.

We tested the hypothesis that compliance with the National Institute for Occupational Safety and Health (NIOSH) heat stress recommendations will prevent reductions in glomerular filtration rate (GFR) across a range of wet-bulb globe temperatures (WBGTs) and work-rest ratios at a fixed work intensity. We also tested the hypothesis that noncompliance would result in a reduction in GFR compared with a work-rest matched compliant trial. Twelve healthy adults completed five trials (four NIOSH compliant and one noncompliant) that consisted of 4 h of exposure to a range of WBGTs. Subjects walked on a treadmill (heat production: approximately 430 W) and work-rest ratios (work/h: 60, 45, 30, and 15 min) were prescribed as a function of WBGT (24°C, 26.5°C, 28.5°C, 30°C, and 36°C), and subjects drank a sport drink ad libitum. Peak core temperature (TC) and percentage change in body weight (%ΔBW) were measured. Creatinine clearance measured pre- and postexposure provided a primary marker of GFR. Peak TC did not differ among NIOSH-compliant trials (P = 0.065) but differed between compliant versus noncompliant trials (P < 0.001). %ΔBW did not differ among NIOSH-compliant trials (P = 0.131) or between compliant versus noncompliant trials (P = 0.185). Creatinine clearance did not change or differ among compliant trials (P ≥ 0.079). Creatinine clearance did not change or differ between compliant versus noncompliant trials (P ≥ 0.661). Compliance with the NIOSH recommendations maintained GFR. Surprisingly, despite a greater heat strain in a noncompliant trial, GFR was maintained highlighting the potential relative importance of hydration.NEW & NOTEWORTHY We highlight that glomerular filtration rate (GFR) is maintained during simulated occupational heat stress across a range of total work, work-rest ratios, and wet-bulb globe temperatures with ad libitum consumption of an electrolyte and sugar-containing sports drink. Compared with a work-rest matched compliant trial, noncompliance resulted in augmented heat strain but did not induce a reduction in GFR likely due to an increased relative fluid intake and robust fluid conservatory responses.

Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes.

Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m2 [-1.33, -1.08] for the general population, "healthy" individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for "healthy" individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for "healthy" individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile.

Reassuring pregnancy outcomes in women with mild COL4A3-5-related disease (Alport syndrome) and genetic type of disease can aid personalized counseling.

Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.

Murine kidney transplant outcome is best measured by transdermal glomerular filtration rate.

Mouse kidney transplantation provides a powerful pre-clinical model for the study of kidney transplant alloimmunity. However, accurate measurement of graft function is difficult by the inaccuracy of traditional surrogate markers serum creatinine and urea. We report the use of transdermal glomerular filtration rate (tGFR) measurement under the experimental conditions of unilateral nephrectomy and allogeneic kidney transplantation. Our findings demonstrate that tGFR measurement is easy to perform, reproducible, and has more inter-experimental consistency in comparison to serum creatinine or urea measurements. Most importantly, it significantly reduces the numbers of experimental animals required to detect subtle and yet clinically relevant differences in kidney function as often is the case in experimental murine kidney transplantation models.

Renal dysfunction in AQP4 NMOSD and MS; a potential predictor of relapse and prognosis.

OBJECTIVE: This study aimed to explore the association between kidney function and the risk of relapse as well as prognosis in patients with aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive neuromyelitis optica spectrum disorder (NMOSD). METHODS: We focused on patients experiencing their first onset of AQP4-IgG-seropositive NMOSD. Data on demographics, disease characteristics, and kidney function were collected, with the primary assessment utilizing the estimated glomerular filtration rate (eGFR). Associations between eGFR and relapse risk were examined using multivariate Cox proportional hazards regression models. Additionally, logistic regression models were employed to evaluate the impact of eGFR on clinical prognosis. RESULTS: Our analysis revealed glomerular hyperfiltration and impaired urine concentrating ability in patients with AQP4-IgG-seropositive NMOSD. Multivariate Cox proportional hazards regression demonstrated a positive correlation between eGFR and the risk of relapse. Logistic regression analysis further identified higher eGFR as an independent predictor of disease relapse and prognosis in AQP4-IgG-seropositive NMOSD patients. CONCLUSIONS: The eGFR of patients with AQP4-IgG-seropositive NMOSD emerges as a potential diagnostic biomarker for this condition, indicating its significance in predicting both relapse risk and clinical prognosis.

Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Causal Relationship Between Kidney Function and Cancer Risk: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Patients treated with kidney replacement therapy experience a 1.5 to 2-fold increased risk of cancer and cancer mortality compared to the general population. Whether this excess risk extends to people with earlier stages of chronic kidney disease is unclear. This study explored the potentially causal relationship between reduced kidney function and cancer. STUDY DESIGN: Two-sample Mendelian randomization (MR). SETTING & PARTICIPANTS: Genome Wide Association Study (GWAS) summary statistics for estimated glomerular filtration rate (eGFR) (n=567,460) and urinary albuminuria (UACR) (n=127,865) from the CKDGen consortium and cancer outcomes from the UK Biobank (n=407,329). EXPOSURES: eGFR and UACR. OUTCOMES: Overall cancer incidence, cancer-related mortality, and site-specific colorectal, lung, and urinary tract cancer incidence. ANALYTICAL APPROACH: Univariable and multivariable MR were conducted for all outcomes using inverse-variance weighted methods. RESULTS: The mean eGFR and median UACR were 91.4 mL/min/1.73m2 and 9.32 mg/g in the CKDGen and 90.4 mL/min/1.73m2 and 9.29 mg/g in the UK Biobank. There were 98,093 cases of cancer, 6,664 colorectal, 3584 lung, and 3,271 urinary tract. There were 15,850 cases of cancer-related death, The genetic instruments for eGFR and UACR comprised 34 and 38 variants, respectively. Genetically predicted kidney function (eGFR and UACR) was not associated with overall cancer risk or cancer death. No associations of genetically predicted eGFR and UACR with overall cancer incidence were observed; odds ratio (95%CI; p-value) of 0.88 (0.40-1.97; p=0.76) and 0.90 (0.78-1.04; p=0.16), respectively. An adjusted generalized additive model for eGFR and cancer demonstrated evidence of non-linearity. There was no evidence of a causal association between eGFR and cancer in a stratified MR. LIMITATIONS: To avoid overlapping samples a smaller GWAS for UACR was used, reducing the strength of the instrument and potentially introducing population stratification. CONCLUSIONS: These findings did not demonstrate a causal association of kidney function with overall cancer incidence or cancer-related death.

A Holistic Framework for the Evaluation of Kidney Function in a Gender-Diverse Landscape.

The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.

Which is the best glomerular filtration marker: Creatinine, cystatin C or both?

BACKGROUND: The glomerular filtration rate (GFR) is estimated by the serum or plasma concentration of creatinine and/or cystatin C using equations that include demographic data. The equations worldwide most widely used are those of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) consortium and updated in 2021 to remove the Afro-American racial correction factor. In 2021 and then in 2023, the European Kidney Function Consortium also developed equations based on creatinine and cystatin C, usable across the full age spectrum, and constructed by including the Q value (i.e. the median creatinine or cystatin C in healthy men and women, which is customizable for specific populations). METHODS: The aim of this narrative review is to examine the strengths and weaknesses of each biomarker. RESULTS: Both biomarkers have non-GFR determinants, namely muscle mass, protein intake and tubular secretion for creatinine; dysthyroidism and systemic corticosteroids for cystatin C, as well as other more debated determinants (diabetes, obesity, proteinuria, inflammatory syndrome). These non-GFR determinants are the reason why no equation based on a single endogenous biomarker has an accuracy within 30% greater than 90% over the entire age spectrum (in at least one patient in 10, estimated GFR is at least 30% higher or at least 30% lower than the measured GFR). CONCLUSION: Equations combining the two biomarkers provide a better estimate of GFR, particularly in the subgroup of patients whose estimates based on each of the biomarkers are highly discordant. These patients must also be identified as being at increased risk of morbidity, particularly cardiovascular, and mortality.

Correlation between Metabolic Parameters and Warfarin Dose in Patients with Heart Valve Replacement of Different Genotypes.

Background: Warfarin has become the first choice for anticoagulation in patients who need lifelong anticoagulation due to its clinical efficacy and low price. However, the anticoagulant effect of warfarin is affected by many drugs, foods, etc. accompanied by a high risk of bleeding and embolism. The Vitamin K epoxide reductase complex 1 (VKORC1) and Cytochrome P450 2C9 (CYP2C9) genotypic variation can influence the therapeutic dose of warfarin. However, it is not clear whether there is a correlation between warfarin dose and liver function, kidney function and metabolic markers such as uric acid (UA) in patients with different genotypes. We performed a single-center retrospective cohort study to evaluate the factors affecting warfarin dose and to establish a dose conversion model for warfarin patients undergoing heart valve replacement. Methods: We studied 343 patients with a mechanical heart valve replacement, compared the doses of warfarin in patients with different warfarin-related genotypes (CYP2C9 and VKORC1), and analyzed the correlation between liver function, kidney function, UA and other metabolic markers and warfarin dose in patients with different genotypes following heart valve replacement. Results: Genotype analysis showed that 72.01% of patients had CYP2C9*1/*1 and VKORC1 mutant AA genotypes. Univariate regression analysis revealed that the warfarin maintenance dose was significantly correlated with gender, age, body surface area (BSA), UA and genotype. There was no correlation with liver or kidney function. Multiple linear regression analysis showed that BSA, genotype and UA were the independent factors influencing warfarin dose. Conclusions: There is a significant correlation between UA content and warfarin dose in patients with heart valve replacement genotypes CYP2C9*1/*1/VKORC1(GA+GG), CYP2C9*1/*1/VKORC1AA and CYP2C9*1/*1/VKORC1AA.

Impact of Postarrest Vasoactive-Inotropic Score on Acute Kidney Injury in Cardiac Arrest Survivors: A Retrospective Cohort Study.

Background: Postarrest acute kidney injury (AKI) is a major health burden because it is associated with prolonged hospitalization, increased dialysis requirement, high mortality, and unfavorable neurological outcomes. Managing hemodynamic instability during the early postarrest period is critical; however, the role of quantified vasopressor dependence in AKI development in relation to illness severity remains unclear. Methods: A retrospective, observational cohort study that enrolled 411 non-traumatic adult cardiac arrest survivors without pre-arrest end-stage kidney disease between January 2017 and December 2019, grouped according to their baseline kidney function. The criteria for kidney injury were based on the Kidney Disease: Improving Global Outcomes definition and AKI staging system. The degree of vasopressor dependence within the first 24 h following return of spontaneous circulation (ROSC) was presented using the maximum vasoactive-inotropic score ( VIS max ). Results: Of the 411 patients, 181 (44%) had early AKI after ROSC. Patients with AKI showed an increased risk of in-hospital mortality (adjusted OR [aOR] 5.40, 95% CI 3.36-8.69, p < 0.001) and unfavorable neurological outcome (aOR 5.70, 95% CI 3.45-9.43, p < 0.001) compared to patients without AKI. The risk of adverse outcomes increased with illness severity. Patients with vasopressor support had an increased risk of early AKI. A low VIS max was associated with AKI stage 1-2 (aOR 2.51, 95% CI 1.20-5.24), whereas a high VIS max was associated with an increased risk for AKI stage 3 (aOR 2.46, 95% CI 1.28-4.75). Conclusions: Early AKI is associated with an increased risk of in-hospital mortality and unfavorable neurologic recovery in cardiac arrest survivors. Postarrest VIS max is an independent predictor of the development and severity of AKI following ROSC, regardless of baseline kidney function.

Apolipoprotein A-IV concentrations and cancer in a large cohort of chronic kidney disease patients: results from the GCKD study.

BACKGROUND: Chronic kidney disease (CKD) is highly connected to inflammation and oxidative stress. Both favour the development of cancer in CKD patients. Serum apolipoprotein A-IV (apoA-IV) concentrations are influenced by kidney function and are an early marker of kidney impairment. Besides others, it has antioxidant and anti-inflammatory properties. Proteomic studies and small case-control studies identified low apoA-IV as a biomarker for various forms of cancer; however, prospective studies are lacking. We therefore investigated whether serum apoA-IV is associated with cancer in the German Chronic Kidney Disease (GCKD) study. METHODS: These analyses include 5039 Caucasian patients from the prospective GCKD cohort study followed for 6.5 years. Main inclusion criteria were an eGFR of 30-60 mL/min/1.73m2 or an eGFR > 60 mL/min/1.73m2 in the presence of overt proteinuria. RESULTS: Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dL (median 27.6 mg/dL). 615 patients had a history of cancer before the enrolment into the study. ApoA-IV concentrations above the median were associated with a lower odds for a history of cancer (OR = 0.79, p = 0.02 when adjusted age, sex, smoking, diabetes, BMI, albuminuria, statin intake, and eGFRcreatinine). During follow-up 368 patients developed an incident cancer event and those with apoA-IV above the median had a lower risk (HR = 0.72, 95%CI 0.57-0.90, P = 0.004). Finally, 62 patients died from such an incident cancer event and each 10 mg/dL higher apoA-IV concentrations were associated with a lower risk for fatal cancer (HR = 0.62, 95%CI 0.44-0.88, P = 0.007). CONCLUSIONS: Our data indicate an association of high apoA-IV concentrations with reduced frequencies of a history of cancer as well as incident fatal and non-fatal cancer events in a large cohort of patients with CKD.

Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.

Real-time estimation of nephron activity with a linear measurement system (RENAL-MS) predicts postoperative estimated glomerular filtration rate.

OBJECTIVE: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression. RESULTS: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting.

Cancer therapy in patients with reduced kidney function.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

The effect of preeclampsia on long-term kidney function among pregnant women with chronic kidney disease.

BACKGROUND AND HYPOTHESIS: The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) has not been determined. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients. METHODS: This was a retrospective cohort study that included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from January 1, 2009, to May 31, 2022. Robust Cox regression analysis was also conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESKD in CKD patients. K-M curves were used to compare renal survival within different subgroups via the log-rank test. RESULTS: During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decrease >30% or developed ESKD. Compared with CKD patients without preeclampsia, the eGFR decreased more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 99.43 (79.00, 118.50) to 89.44 (63.69, 105.30) mL/min/1.73 m2; P=0.034]. The rate of eGFR decrease was more pronounced in patients with preeclampsia (17.38% vs. 10.05%, p<0.05). Multivariate analysis revealed that early-onset preeclampsia (preeclampsia that developed before 34 weeks of gestation) (HR=2.61, 95% CI=1.32-5.16, P=0.006) and late-onset preeclampsia (HR=2.54, 95% CI=1.34-4.83, P=0.004) were both risk factors for an eGFR decrease >30% or ESKD. CONCLUSION: Preeclampsia was associated with a greater risk of long-term kidney function decline or ESKD among CKD patients, especially in patients with early-onset preeclampsia.